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Among the viruses possibly responsible for hospital-acquired and ventilator-associated pneumonia, herpes simplex virus (HSV) is probably the most often involved: HSV reactivation is frequent in intensive care unit patients, and lung parenchymal infection (HSV bronchopneumonitis) has been well described, either using cytological signs of parenchymal involvement in cells obtained during bronchoalveolar lavage or using HSV virus load in the lower respiratory tract. Although treating patients with HSV bronchopneumonitis may be recommended, based on expert opinion, prophylactic or preemptive treatment of HSV reactivation should be avoided. Ventilator-associated pneumonia due to cytomegalovirus (CMV) is less frequent than HSV bronchopneumonitis, and more difficult to diagnose. No data exists on the impact of antiviral treatment on CMV pneumonia. The involvement of respiratory viruses has been described in patients with healthcare-associated pneumonia and hospital-acquired pneumonia, but their role in ventilator-associated pneumonia is not clear.

Critically ill patients are admitted to an intensive care unit (ICU) for multiple reasons. In this study, we aim to analyze the current evidence and findings associated with influenza and other emergent viral infections, namely, herpes simplex virus type 1 (HSV-1), Epstein-Barr virus (EBV), and cytomegalovirus (CMV).Among medical conditions, community-acquired respiratory infections are the most frequent reason for ventilatory support in ICUs. Community-acquired pneumonia in a severe form including the need of invasive mechanical ventilation and/or vasopressors is associated with high mortality rates. However, after the pandemic that occurred in 2009 by H1N1 influenza, the number of cases being admitted to ICUs with viral infections is on the rise. Patients in whom an etiology would not have been identified in the past are currently being tested with more sensitive viral molecular diagnostic tools, and patients being admitted to ICUs have more preexisting medical conditions that can predispose to viral infections. Viral infections can trigger the dysregulation of the immune system by inducing a massive cytokine response. This cytokine storm can cause endothelial damage and dysfunction, deregulation of coagulation, and, consequently, alteration of microvascular permeability, tissue edema, and shock. In severe influenza, this vascular hyperpermeability can lead to acute lung injury, multiorgan failure, and encephalopathy. In immunocompetent patients, the most common viral infections are respiratory, and influenza should be considered in patients with severe respiratory failure being admitted to ICU. Seasonality and coinfection are two important features when considering influenza as a pathogen in critically ill patients.Herpesviridae (HSV, CMV, and EBV) may reactivate in ICU patients, and their reactivation is associated with morbidity/mortality. However, whether a specific treatment may impact on outcome remains to be determined.

Morbidity, mortality, and economic burden of nosocomial pneumonia caused by Staphylococcus aureus and Pseudomonas aeruginosa remain high in mechanically ventilated and hospitalized patients despite the use of empirical antibiotic therapy or antibiotics against specific classes of pathogens and procedures to reduce nosocomial infections in hospital settings. Newer agents that neutralize or inhibit specific S. aureus or P. aeruginosa virulence factors may eliminate or reduce the risk for developing pneumonia before or during mechanical ventilation and may improve patient outcomes through mechanisms that differ from those of antibiotics. In this article, we review the types, mechanisms of action, potential advantages, and stage of development of antivirulence agents (AVAs) that hold promise as alternative preventive or interventional therapies against S. aureus– and P. aeruginosa–associated nosocomial pneumonias. We also present and discuss challenges to the effective utilization of AVAs separately from or in addition to antibiotics and the design of clinical trials and meaningful study end points.

Ventilator-associated pneumonia (VAP) is the most frequent intensive care unit (ICU)-acquired infection among patients receiving mechanical ventilation. Consensus, however, on the most appropriate diagnostic strategy for patients clinically suspected of having developed VAP has yet to be reached. Concern about the inaccuracy of clinical approaches to VAP recognition and potential for excessive use of antibiotics in the ICU had led numerous investigators to postulate that quantitative cultures of specimens obtained with bronchoscopic or nonbronchoscopic techniques, such as bronchoalveolar lavage (BAL) and/or protected specimen brush (PSB), could improve identification of patients with true VAP and facilitate decisions whether to treat. Other than decision-analysis studies and one retrospective study, only five trials assessed the impact of such a quantitative bacteriological strategy on antibiotic use and outcome of patients suspected of VAP using a randomized scheme. In one study, the invasive management strategy was significantly associated with earlier attenuation of organ dysfunction and less antibiotic exposure, but the four other trials could not replicate these positive findings, including a large Canadian study that enrolled 740 patients. Because antibiotics were continued in most patients with negative BAL cultures in contradiction with the bacteriological algorithm, additional studies will be needed before concluding that a strategy based on the systematic collection of distal pulmonary secretions before introduction of new antibiotics and quantitative culture techniques is useless and cannot prevent the overuse of antimicrobial agents in the ICU.

Procalcitonin's contribution to the diagnosis of nosocomial infection, particularly ventilator-associated pneumonia (VAP), is poor: its levels in patients with microbiologically documented VAP the day infection is diagnosed range from normal to extremely high. Moreover, the results of four studies showed that, despite relatively good specificity, this marker had low sensitivity for the diagnosis of VAP. However, because procalcitonin is well associated with outcome, its kinetics during antimicrobial therapy can be used to customize that treatment duration. Two recent studies showed that a procalcitonin-based strategy (recommending that treating physicians stop antibiotics when the procalcitonin concentration was

Since antibiotic resistance has become a worldwide concern, there has been an ongoing debate as to whether infections caused by resistant bacteria are associated with higher mortality. Because resistant strains do not appear to be more virulent, differences in outcome may principally relate to patients' characteristics before or at the time of infection onset, and to high rates of inappropriate empirical antimicrobial treatment prescribed for antibiotic-resistant infections. In two large series of severe Staphylococcus aureus and Pseudomonas aeruginosa ventilator-associated pneumonia, we recently demonstrated that antibiotic resistance does not significantly affect intensive care unit mortality of patients receiving appropriate initial antibiotics. However, antibiotic resistance was consistently found to increase hospital length of stay. Early identification of patients with risk factors favoring antibiotic-resistant infections should prompt the initiation of an empirical antibiotic regimen covering these highly resistant bacteria, which can usually be deescalated 48 to 72 hours later when the results of microbiological samples culture become available.